Advanced Hepatocellular Carcinoma With c-MET Dysregulation Clinical Trial
Official title:
A Phase II, Open Label, Single Arm, Multicenter Study of INC280 Administered Orally in Adults With Advanced Hepatocellular Carcinoma
| Verified date | July 2023 |
| Source | Novartis |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
This study is to find out if INC280 is safe and has beneficial effects in patients with advanced hepatocellular carcinoma known to have dysregulation of c-MET pathway.
| Status | Terminated |
| Enrollment | 38 |
| Est. completion date | May 24, 2023 |
| Est. primary completion date | April 24, 2023 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | Inclusion Criteria: - Confirmed c-MET pathway dysregulation. - Advanced hepatocellular carcinoma which could not be suitable for treatment with locoregional therapies or has progressed following locoregional therapy. - Measurable disease as determined by RECIST version 1.1. - Current cirrhotic status of Child-Pugh class A with no encephalopathy. - Eastern Cooperative Oncology Group (ECOG) performance status < or = 2. - Other protocol-defined inclusion criteria may apply. Exclusion Criteria: - Received any prior systemic chemotherapy or molecular-targeted therapy for hepatocellular carcinoma such as sorafenib. - Previous treatment with c-MET inhibitor or hepatocyte growth factor targeting therapy. - Previous local therapy completed less than 4 weeks prior to dosing and, if present, any acute toxicity > grade 1. - Known active bleeding (e.g. bleeding from gastro-intestinal ulcers or esophageal varices) within 2 months prior to screening or with history or evidence of inherited bleeding diathesis or coagulopathy. - Clinically significant venous or arterial thrombotic disease within past 6 months. - History of acute or chronic pancreatitis, surgery of pancreas or any risk factors that may increase risk of pancreatitis. - Other protocol-defined exclusion criteria may apply. |
| Country | Name | City | State |
|---|---|---|---|
| China | Novartis Investigative Site | Hangzhou | Zhejiang |
| China | Novartis Investigative Site | Nanjing | Jiangsu |
| China | Novartis Investigative Site | Xi'an | Shanxi |
| Hong Kong | Novartis Investigative Site | Hong Kong | |
| Singapore | Novartis Investigative Site | Singapore | |
| Thailand | Novartis Investigative Site | Bangkok | |
| Thailand | Novartis Investigative Site | Bangkok | |
| Thailand | Novartis Investigative Site | Khon Kaen | THA |
| Lead Sponsor | Collaborator |
|---|---|
| Novartis Pharmaceuticals |
China, Hong Kong, Singapore, Thailand,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Time to progression using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 | Time to progression is the time from the date of baseline evaluation to the date of the first documented radiological confirmation of disease progression or death due to underlying cancer. | Average of 6 weeks, up to 8 years | |
| Secondary | Overall Response Rate | Overall Response Rate is defined as the proportion of patients with a best overall response of complete response or partial response at any time on study per RECIST version 1.1. | Average of 6 weeks, up to 8 years | |
| Secondary | Progression free survival | Progression free survival is defined as the time from date of first study treatment intake to the date of the first radiologically documented progression or death due to any cause or initiation of new antineoplastic therapy. if a patient has not had an event, progression free survival is censored at the date of last adequate tumor assessment. | Average of 6 weeks, up to 8 years | |
| Secondary | Overall survival | Overall survival is defined as the time from date of first study treatment intake to the date of death due to any cause. If a patient is not known to have died, survival will be censored at the date of last contact. | Average of 6 weeks, up to 8 years | |
| Secondary | Disease Control Rate | Disease control rate is defined as the proportion of patients with a best overall response of complete response, partial response or stable disease at any time on study per RECIST version 1.1 | Average of 6 weeks, up to 8 years | |
| Secondary | Safety: adverse events, serious adverse events | Frequency and severity of adverse events. | Average of 6 weeks, up to 8 years | |
| Secondary | Number of participants with dose interruptions and dose reductions | Number of participants with at least one dose interruption of INC280 and number of participants with at least one dose reduction of INC280. | Average of 6 weeks, up to 8 years | |
| Secondary | Dose intensity | Dose intensity is defined as the ratio of actual cumulative dose received and actual duration of exposure. | Average of 6 weeks, up to 8 years | |
| Secondary | Plasma pharmacokinetic parameter: AUC0-t | Plasma concentration of INC280 versus time profiles. AUC=Area Under the Curve | Days 1, 2, 15 and 16 of Cycle 1, Day 1 of Cycle 2 and Cycle 3 | |
| Secondary | Plasma pharmacokinetic parameter: CL/F | Plasma concentration of INC280 versus time profiles | Days 1, 2, 15 and 16 of Cycle 1, Day 1 of Cycle 2 and Cycle 3 | |
| Secondary | Plasma pharmacokinetic parameter: Cmax | Plasma concentration of INC280 versus time profiles. Cmax = Maximum concentration | Days 1, 2, 15 and 16 of Cycle 1, Day 1 of Cycle 2 and Cycle 3 | |
| Secondary | Plasma pharmacokinetic parameter: Tmax | Plasma concentration of INC280 versus time profiles. Tmax =Time to reach maximum concentration | Days 1, 2, 15 and 16 of Cycle 1, Day 1 of Cycle 2 and Cycle 3 | |
| Secondary | Plasma pharmacokinetic parameter: T1/2 | Plasma concentration of INC280 versus time profiles | Days 1, 2, 15 and 16 of Cycle 1, Day 1 of Cycle 2 and Cycle 3 | |
| Secondary | Plasma pharmacokinetic parameter: Racc | Plasma concentration of INC280 versus time profiles | Days 1, 2, 15 and 16 of Cycle 1, Day 1 of Cycle 2 and Cycle 3 |